Efficient functioning of the immune system requires a fine balance between cell proliferation and differentiation and cell death, to ensure that the immune system is capable of reacting to foreign, but not self antigens. Regulation of the immune system occurs by the interaction of numerous receptor/ligand pairs, some of which have been identified and their functions delineated. However, there are molecules that are known to be present on or expressed by cells involved in an immune response, but for which a function (or functions) and/or binding partner is not known.
One such molecule is referred to as OX2; it has been identified on a variety of cells, including B and T lymphocytes, neurons, follicular dendritic cells, endothelial cells and thymocytes (Barclay et al., Immunol. 44:727; 1981). OX2 is a transmembrane protein comprising two immunoglobulin (Ig) domains and a short cytoplasmic domain that is thought to be a ligand for a receptor (Clark et al., EMBO J. 4:113; 1985). OX2 has been designated the human leukocyte antigen CD200 (HLDA7: 7th Workshop and Conference on Human Leukocyte Differentiation Antigens, Harrogate, UK, 20 to 24 Jun. 2000).
A counterstructure for OX2 was identified in rat splenic lysates using a monoclonal antibody, and the cDNA encoding this counterstructure (also referred to as OX2 receptor or OX2R) was isolated (Wright et al., Immunity 13:233; 2000). The counterstructure was found to be a transmembrane protein which, like OX2, comprised two Ig domains; the cytoplasmic domain, however, was longer than that of OX2 and included a motif common to other receptors that bind signaling adaptor molecules, including beta integrins (Patil et al., J. Biol. Chem. 274:28575; 1999). Human homologs of the rat OX2R were identified by Barclay et al. (WO 00/70045, published Nov. 23, 2000).
The OX2R, unlike OX2/CD200, exhibited limited distribution, with expression limited to cells of the myeloid lineage (Wright et al., supra; Preston et al., Eur. J. Immunol. 27:1911, 1997). Moreover, the lack of OX2/CD200 in gene-targeted mice led to enhanced susceptibility to experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA), both of which are models for human autoimmune disease (Hoek et al., Science 290:1768; 2000). Taken together, these results imply an important role for OX2R/CD200R in the regulation of myeloid lineage cells, and hence, the immune response. Accordingly, there is a need in the art to identify additional forms of human OX2R/CD200R, particularly soluble forms that can be used in therapeutic or diagnostic applications.